P1423: GENOTYPE GUIDED DISEASE MANAGEMENT IN HBSC SICKLE CELL DISEASE USING PHLEBOTOMY: IMPACT ON SYMPTOMS AND DISEASE PARAMETERS
Authors: Anne-Marie Asemissen, Feline von Feldmann, Roswitha Dickerhoff, Corinna Güsmer, Carsten Bokemeyer, Thorben Mährle
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: The term sickle cell disease (SCD) includes different genotypes. HbSC disease is one of the most common compound hemoglobinopathies in persons of West African decent. The clinical presentation of HbSC is very different compared to homozygous sickle cell disease. The pathology is driven by high blood viscosity and erythrocyte dehydration and results more often in hearing loss, proliferative retinopathy and osteonecrosis compared to HbSS. High-quality data and evidence-based guidelines for genotype specific management of HbSC are lacking. Based on retrospective clinical data, some guidelines recommend phlebotomy (PT) for improvement of acute and chronic pain and tissue damage in patients (pts) with HbSC. In addition, pts with sickle cell disease benefit from iron depletion. Therefore, we have offered PT to symptomatic pts with HbSC disease. Aims: Improve symptoms and outcome in persons with HbSC disease by genotype guided management. Methods: We performed a retrospective monocentric analysis. Disease parameters were collected from all pts who presented at least once during the observation period. In continuously treated pts follow up data were obtained for symptom burden, hemolysis parameters, organ function with a baseline assessment before July 1, 2021 and follow up data obtained at least one year later. Results: Of 100 pts included in the analysis, 27 had HbSC disease. All persons with HbSC came from West African decents. The median age was 32 years (range 19-56 years), 12 (45%) pts were female. Of the 27 pts with HbSC disease, 21 were included in the follow up analysis. Median Hb at baseline was 12 g/dl (range 9-14), MCV was 85 fl (64-110), LDH was 323 U/l (198-464), bilirubin 1,3 mg/dl (0,7-3,1) and ferritin was 68 ug/l (9-315). No one of the pts received PT before, and 12 pts (57%) received Hydroxycarbamid (HC). Most common disease complications were VOC in 90%, retinopathy in 62%, hearing loss in 38% and osteonecrosis in 24% of pts. We stopped HC-treatment and offered PT in all symptomatic HbSC patients with an Hb >10 g/dl. Repeated PT was performed in 16/21 (76%) of pts. A blood loss of 500 ml was targeted followed by fluid substitution every 7 to 14 days until a stable Hb <10 g/dl was achieved. Following repeated PT there was a significant reduction of Hb (median 11 g/dl, range 7-12, p< 0,001), MCV (73 fl, 57-98; p=0,002), ferritin (19 ug/l, 5-175; p=0,002). We observed an improvement of hemolytic parameters (reduction of LDH and bilirubin (243 U/l, 148-414; p=0,04 and 1,1 mg/dl, 0,4-2,2; p= 0,007, respectively). No decrease in GFR was observed and proteinuria was resolved in one pt. All pts reported improvement or complete resolution of pain during or following PT. In one pt with recurring stuttering priapism, immediate relieve of symptom was achieved whenever PT was performed. Several pts reported an improvement of fatigue. One female pt had symptomatic iron deficiency following PT but decided to continue PT with intermittend iron substitution. No one reported symptomatic anemia, dizziness or hypotension after PT. Summary/Conclusion: PT for symptomatic HbSC disease was highly accepted and resulted in impressive improvement of pain, fatigue and also priapism in one pt. The observation period is too short to assess long term stabilization of hearing loss and relapse of retinopathy in our pt cohort. Prospective clinical trials are needed to validate optimal targeted, genotype-guided management in people with HbSC disease, especially onset of PT in adolescence to prevent endorgan damage especially in young patients. Keywords: Genotype, Sickle cell disease